Enhanced interstitial fluid collection

ABSTRACT

A sampling apparatus for interstitial fluid includes a pressure ring surrounding a collection needle. The pressure ring and needle are movable relative to one another for the ring to first engage a patient&#39;s skin surface prior to insertion of the needle.

I. CROSS-REFERENCE TO RELATED APPLICATION

The present application discloses and claims subject matter disclosed inconcurrently filed and commonly assigned U.S. patent application Ser.No. ______ entitled “Interstitial Fluid Sampler”.

II. BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention pertains to an apparatus for testing body fluidconstituents. More particularly, this invention pertains to an apparatuswith enhanced interstitial fluid collection.

2. Description of the Prior Art

In the prior art, there are numerous examples of apparatus for testingand determining the level of constituents in human blood. A great dealof attention has been directed to the development of techniques andapparatus for measuring blood glucose.

As noted in commonly assigned and co-pending U.S. patent applicationSer. Nos. 08/321,305 and 08/136,304 (corresponding to PCT InternationalPublication No. WO95/10223 published Apr. 20, 1995 on InternationalApplication No. PCT/US94/11580 and incorporated herein by reference),the determination of the level of a constituent of blood can be achievedby measuring the level of that constituent in other body fluids such asinterstitial fluid. The aforementioned patent applications andinternational publication disclose a method and apparatus for aminimally invasive technique for collecting a sample of interstitialfluid through use of an extremely small needle which penetrates into thedermal layer of the skin in order to collect a low blood or blood-freesample of interstitial fluid. The collected interstitial fluid can thenbe analyzed for a determination of the level of constituents within thefluid. For example, the collected interstitial fluid can be analyzed foran amount of glucose with the determined amount being representative ofthe amount of glucose contained within the patient's blood.

The aforementioned applications and international publication disclosethe use of a ring (item 60 in FIG. 6 of the application) which surroundsthe needle to create a pressure area on the patient's skin. It isbelieved this leads to increase the amount of interstitial fluid beingcollected.

In the collection of interstitial fluid, it is desirable to increase thespeed at which a sample is collected. In the absence of mechanical orother assistance, the rate at which interstitial fluid is collectedthrough a small diameter tube or needle is very slow. Preferably,patients utilizing such equipment for home use, will be provided with asystem which collects interstitial fluid at a rapid pace to ensure thata patient does not remove the needle too early in its application. Also,it is important to provide for techniques to increase a volume ofinterstitial fluid being collected through a needle.

When collecting any body fluid through use of a needle, it is importantthat the needle be a disposable item in order to prevent re-use of theneedle. Such re-use can result in the transmission of disease. Where theapparatus is to be used in a patient's home by the patient, theapparatus should be simple to use and with the needle incorporated in adisposable item. Since the needle is incorporated in a disposable item,it is important that the disposable item be amenable to low-costmanufacture. Also, in order to test the interstitial fluid, theinterstitial fluid collection mechanism must be coupled with an analyticmechanism for analyzing the collected fluid. Where such a device is tobe used in home by low-skilled patients, it is important that thesampler and the analytic portion of the device be mutually configured toensure that the sampler is coupled to the apparatus in a repeatable andreliable manner to minimize errors resulting from use of the apparatusby untrained patients.

III. SUMMARY OF THE INVENTION

According to a preferred embodiment of the present invention, a samplerfor collecting interstitial fluid from a skin layer is disclosed. Thesampler includes a sampling needle having an axis and terminating at adistal end. A pressure ring surrounds the needle in spaced relation tothe needle. The needle and the pressure ring are movable relative to oneanother along a path of travel which is generally parallel to the axisof the needle. The needle and ring are movable relative to one anotherbetween an extended position and a retracted position. In the extendedposition, the distal end of the needle extends beyond the ring. In theretracted position, the distal end of the needle is recessed behind thering. A spring is provided for biasing the needle and the ring to theretracted position.

IV. BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional elevation view of an interstitial fluidapparatus showing a sampler contained within the apparatus in aretracted position;

FIG. 2 is the view of FIG. 1 with the apparatus shown in an extendedposition;

FIG. 3 is a perspective exploded view of the apparatus of FIG. 1;

FIG. 4 is the view of FIG. 3 rotated 90° to the right of the view ofFIG. 3;

FIG. 5 is the view of FIG. 4 rotated 90° to the right of FIG. 4;

FIG. 6 is the view of FIG. 5 rotated 90° to the right of FIG. 5;

FIG. 7 is a perspective view of an optics housing for use in theapparatus of FIG. 1;

FIG. 8 is a side elevation view of the housing of FIG. 7;

FIG. 8A is an enlarged view of a bottom portion of the view of FIG. 8;

FIG. 9 is a side elevation view of the housing of FIG. 7 rotated 90°from the view of FIG. 8;

FIG. 10 is a view taken along line 10-10 of FIG. 9;

FIG. 11 is a bottom plan view of the housing of FIG. 7;

FIG. 12 is a perspective view of a shell for use in the apparatus ofFIG. 1;

FIG. 13 is a sectional view of the shell of FIG. 12;

FIG. 14 is a perspective view of a collar for use in the apparatus ofFIG. 1;

FIG. 15 is a sectional view of the collar of FIG. 14;

FIG. 16 is a perspective view of a base for use in the apparatus of FIG.1;

FIG. 17 is a sectional view of the base of FIG. 16;

FIG. 18 is a top, left side and rear end exploded perspective view of asampler for use in the apparatus of FIG. 1;

FIG. 19 is a top, left side and rear end perspective view of a samplermain body for the sampler of FIG. 18;

FIG. 20 is a left side elevation view of the sampler main body of FIG.18 (with the opposite side being substantially identical);

FIG. 21 is a view taken along line 21-21 of FIG. 20;

FIG. 22 is a view taken along line 22-22 of FIG. 20;

FIG. 23 is an enlarged bottom view of a front portion of the main bodyof FIG. 20;

FIG. 24 is a side elevation view of a piston for the sampler of FIG. 18;

FIG. 25 is a view taken along line 25-25 in FIG. 24;

FIG. 26 is a side elevation view of a catch pin for the sampler of FIG.18;

FIG. 27 is a view taken along line 27-27 in FIG. 26;

FIG. 28 is a schematic representation showing the apparatus of FIG. 1placed against a patient's skin;

FIG. 29 is the view of FIG. 28 showing initial forcing of the apparatusagainst the patient's skin;

FIG. 30 is the view of FIG. 28 showing urging of the apparatus againstthe patient's skin with penetration of a needle into the patient's skinlayer and with a piston aligned with a pressure ring; and

FIG. 31 is the view of FIG. 28 with the piston protruding beyond thepressure ring.

V. DESCRIPTION OF THE PREFERRED EMBODIMENT

With reference now to the various drawing figures in which identicalelements are numbered identically throughout, a description of thepreferred embodiment of the present invention will be shown. While theinvention will be described with reference to an apparatus forcollecting interstitial fluid to test for glucose within theinterstitial fluid, it will be appreciated that the apparatus can beused for testing any body constituent which may be contained withininterstitial fluid.

In a preferred embodiment, the apparatus is disclosed with reference touse of a penetrating needle and an absorbing membrane such as that shownand described in U.S. patent application Ser. Nos. 08/321,305 and08/136,304 (and corresponding PCT International Publication No. WP95/10223, dated Apr. 20, 1995 on International Application No.PCT/US94/11580, incorporated herein by reference). With reference toFIGS. 16-20 of that application (showing a representative embodiment ofthe invention shown in that application), a needle 214′ is surroundedand maintained in fixed relative position by a ring 202′. The ring isplaced against a patient's skin in order to define a pressurized area onthe patient's skin as the needle 214′ penetrates into the skin. Theneedle is sized to be about 28 to 32 gauge (i.e., 0.36 mm outsidediameter to 0.23 mm outside diameter) with an anticipated preferred sizeof about 30 gauge. The needle is made as small as possible to provide aminimally intrusive and painless insertion into the skin. The needle issized to penetrate into the dermis for a variety of reasons as bestdisclosed in the aforementioned application including low pain and thecollection of low blood interstitial fluid for subsequent testing. Anabsorbent membrane 210′ is placed in fluid flow communication with theneedle 214′ such that interstitial fluid which flows through the needle214′ is deposited on the membrane 210′ as a spot available forsubsequent testing with light (visible or non-visible spectrum). Theamount of absorption of various wavelengths of the light indicating theconcentration of constituents for testing such as glucose or the like.

The present invention pertains to a testing apparatus which includes aneedle 10 disposed in fluid flow communication with an absorbentmembrane 12 both in accordance with the teachings of the aforementionedPCT International Publication No. WO95/10223.

The present invention is directed to an apparatus 20 (FIGS. 1-6) forcollecting and testing interstitial fluid. The apparatus 20 includes amain housing 22 (shown in FIGS. 1 and 2 only) coupled to a base 24. Theapparatus 20 further includes a collar 26 secured to the base 24. Ashell 28 is contained within the collar 26. An optics housing 30 iscontained within the shell 28. Finally, a sampler 32 is provided to bereceived within the optics housing 30. Each of base 24, collar 26, shell28, optics housing 30 and sampler 32 will be separately described.

Main housing 22 is shown only in section in FIGS. 1 and 2. Main housing22 is sized to be gripped by a patient such that the apparatus 20 may beurged against the patient's skin for purpose of collecting interstitialfluid as will be described. In addition to constituting a handle whichcan be grasped by the patient, the main housing 22 will containelectronics and the like for generating power for a light source as willbe described and for analyzing signals from a light detector (as will bedescribed) in order to calculate the level of constituents, such asblood glucose, contained within a sample of interstitial fluid. Suchelectronics are not shown but it will be appreciated that suchelectronics are well within the skill of the art. Examples of circuitsfor analyzing sampling light are described in commonly assigned U.S.Pat. No. 5,115,133 to Knudson dated May 19, 1992 and the aforementionedInternational Publication No. WO95/10223.

The base 24 is separately shown in FIGS. 16 and 17. Base 24 issubstantially cylindrical and is provided with an end plate 36 havingholes 38 extending at least partially therethrough with the holes 38sized to receive any suitable fastening means such as bolts or the likefor fastening of the end plate 36 to the main housing 22. The base 24further includes an inner hollow cylinder 40 extending from plate 36with the inner cylinder 40 being coaxial with an outer cylinder 42 ofthe base 24. Outer cylinder 42 has a threaded inner surface 44.

The collar 26 is separately shown in FIGS. 14 and 15. The collar 26includes an enlarged cylindrical portion 50 sized to be received withinbase 24 and with an end 51 abutting the end plate 36 of base 24. Anouter wall 52 is threaded to mate with the internal threading 44 of base24. An inner wall 53 of cylindrical portion 50 remains spaced from innercylinder 40 to define a void for receiving springs as will be described(and as shown in FIGS. 1-2). The collar 26 also includes a reduceddiameter portion 54 with the reduced diameter portion 54 and theenlarged diameter portion 50 connected at an annular stop surface 56shown in FIG. 15. For purposes that will become apparent, the reduceddiameter portion 54 includes a slot 58 at an end 59 of portion 54.Linearly aligned with slot 58 is a hole 61.

The shell 28 is separately shown in FIGS. 12 and 13. The shell 28includes a cylindrical body 60 sized to be slidably received in closetolerance within the reduced diameter cylindrical portion 54 of collar26. The cylindrical body 60 terminates at a flange 62 positioned to abutstop surface 56 of collar 26. Accordingly, the shell 28 is slidablewithin the collar 26 with the flange 62 movable between the stop surface56 of collar 26 and the end plate 36 of base 24.

The cylindrical body 60 has at its end opposite flange 62 a reduceddiameter portion 64 which is coaxial with the main cylindrical body 60.The reduced diameter portion 64 terminates at a first pressure ring 66with the plane of the opening of the pressure ring 66 being generallyperpendicular to the cylindrical axis of body 60. An elongated slot 68extending generally in the direction of the axis of body 60 is providedextending through the shell 28 with the slot 68 extending substantiallythe length of the body 60 and substantially the length but not entirelythrough the sidewall of the reduced diameter portion 64 such that ring66 is an uninterrupted ring. However, a segmented ring or otherincomplete ring would be satisfactory.

The optics housing 30 is separately shown in FIGS. 7-11 and includes agenerally cylindrical main body 70 (with flat side walls 71 a, 71 b)having extending axially therefrom a reduced diameter cylinder 72(surrounded by surface 71) having an annular slot 73. The reduceddiameter cylinder 72 is sized to be slidably received within the innercylinder 40 of base 24 as best shown in FIGS. 1 and 2.

The main body 70 includes a first axial slot 74 extending partiallythrough a distal end 75 of the body 70. Disposed axially spaced fromslot 74 is a second slot 76 extending through the main body 70. A pinreceiving hole 77 extends through body 70 perpendicular to slot 76.Ninety degrees offset from slots 74, 76 are access holes 78 incommunication with a hollow interior 80 of cylinder 72. Ninety degreesoffset from slot 74 are pockets 82, 83 with axes of the pockets 82, 83in coaxial alignment with one another and in communication with the slot74. The base end 75 has a ramped ridge 79 extending parallel to hole 77.

In the assembly, as best shown in FIGS. 1 and 2, a first biasing spring84 is positioned to act between the base plate 36 of base 24 and theflange 62 of shell 28 urging the shell 28 away from the base plate 36. Asecond biasing spring 86 is positioned to act against the base plate 36of base 24 and an engaging surface 71 on cylinder 70 thereby urging theoptics housing 30 axially away from the base plate 36.

As shown in FIGS. 3-6, a light source 90 is contained within pocket 82.A light detector 92 is contained within pocket 83. Electrical leads (notshown) from both the light source 90 and light detector 92 may be passedbetween the opposing exterior surfaces 71 a, 71 b of cylinder 70 and theinterior surface of shell cylinder 60 with the leads then passed throughthe holes 78, into hollow interior 80 of cylinder 72 and directed thusinto the circuitry (not shown) contained within the housing 22. Thelight source 90 and light detector 92 are aligned to define a light paththerebetween. The light source 90 generates a testing wavelength. Thelight detector 92 is selected to measure the intensity of wavelengthsincluding the intensity of the testing wavelength.

A lock pin 94 (shown separately in FIGS. 26-27) is contained withinoptics housing 30 in hole 77 with the lock pin 94 positioned at a 900angle to the plane of the slot 74. The pin 94 has a ramp 95 disposed inslot 76. In the assembly shown in FIGS. 1-6, the slots 74, 76 of theoptics housing 30 are in alignment with the slot 68 of the shell 28.

As shown in FIGS. 18-25, the sampler 32 includes a body 100 formed ofinjection molded plastic. The body 100 includes a rear handle portion101 and a forward sampling portion 102. The handle portion 101 is sizedto be gripped by the fingers of a user. At the sampling end 102, thebody 100 is provided with a hub or piston 104. The piston 104 iscylindrical and sized to be received in close sliding tolerance withinthe reduced diameter cylinder 64 of shell 28. The piston terminates at aflat second pressure surface 106 which is generally perpendicular to theaxis of the needle 10. While a flat surface 106 is preferred, othershapes (e.g., concave) could be used.

The needle 10 protrudes beyond the surface 106 a distance equal to adesired penetration of the needle 10 into a patient's skin layer. Asdisclosed in the aforementioned international publication, distance ofprotrusion of needle 10 is about 1.5 mm to ensure protrusion of theneedle 10 into but not through a dermal layer of a patient's skin. Atthe sampling end 102, the main body 100 is provided with a relief 108surrounding a hole 110 formed through the body. The hole 110 is incommunication with a proximal end 11 of the needle 10. Accordingly, anabsorbent material 12 such as the material 210′ shown in FIGS. 16-20 ofthe aforementioned International Publication No. WO95/10223 may beplaced within the relief 108 such that interstitial fluid which flows upthe needle 10 will be deposited upon the membrane 12. The membrane 12 isheld in place through any suitable means such as by an adhesive ring 111(or, alternatively, ultrasonic bending or other bonding technique).

The hole 110 is positioned at a sampling location such that the hole 110is in the light path between the light source 90 and the light detector92 when the sampler 32 is placed within the apparatus 20 as will bedescribed. The end 102 is sized to be received within the aligned slots68, 74 of shell 28 and optics housing 30, respectively.

The main body 100 is provided with an arcuate rib 113 sized and shapedto abut an exterior surface of the optics housing 30 on both sides ofthe slot 74 and to curve beneath the base 75. A latching member 112 isconnected to the body 100. The latching member 112 pivots at a point ofconnection to the body 100 and includes a lever arm 114 exposed at thehandle portion 101 such that the lever member 114 may be depressed by auser. The latch 112 further includes a latching end 116 sized andpositioned to be received within the hole 76 of the optics housing 30.The latching end 116 includes a detent 118 (FIGS. 1-2) positioned toengage and receive the ramp 95 of the lock pin 94 within the detent 118when the sampler 32 is inserted within the slots 74, 76 in apredetermined alignment and with the sampling location 110 disposedwithin the light path between the source 90 and detector 92. A leadingend of the locking end 116 is provided with a ramped surface to rideover the pin 94 upon insertion of the sampler 32 within the opticshousing 30 and to provide a positive lock as the pin is received withinthe detent 118. To further secure the sampler 32 in optics housing 30 inthe desired alignment, sampler housing 100 has a detent 117 (FIG. 23) toreceive ridge 79 on the base 75 of optics housing 30. The sampler 32 maybe easily removed by a user depressing end 114 thereby raising end 116for the pin 94 to clear the detent 118 permitting removal of the sampler32 from the apparatus.

With the construction thus described, a sampling end 102 may be placedwithin the aligned slots 74, 68. Over-insertion is avoided by reason ofthe sampling end 102 butting up against the interior of the opticshousing 30. Further, the lock pin 94 received within the detent 118 andthe ridge 79 in detent 117 ensure that the sampler 32 is notunder-inserted into the slots 74, 76 by providing a user with a positivefeedback indicating that the lock pin 94 has been received within thedetent 118 indicating the sampler 32 is in the predetermined alignment.Accordingly, upon receipt of such feedback, the user is assured that thesampling location 110 is in alignment with the light path between thelight source 90 and the light detector 92.

The first spring 84 urges the shell away from the base 24 such that thefull length of the piston 104 and needle 10 may clear the first pressurering 66 and be inserted through the slot 68 as the sampler 32 is loadedinto apparatus 20.

Due to the locking at detents 118 and 117, sampler 32 is held in apredetermined alignment with the membrane 12 in the light path betweenlight source 90 and light detector 92. To facilitate placement ofsampler 32 within apparatus 20, the sampler 32 and apparatus 20 havemating external geometries. Namely, in the rest position of FIG. 1, theshell 28 is fully extended from base 36 by spring 86. Slot 58 of collar26, slot 68 of shell 28 and slot 74 of optics housing 30 are aligned topermit insertion of end 102 of sampler 32. Further, in this position,slot 68 is sized so that needle 10 may pass ring 66 withoutinterference. Also, in this position, slot 61 of collar 26, slot 68 ofshell 28 and hole 76 of optics housing 30 are aligned to receive end 116of lever arm 112.

Upon insertion, the mating geometry of sampler 32 and optics housing 30insure the membrane 12 is accurately positioned. The ribs 113 actingagainst the external surface of optics housing 30 together with ribs 95,79 received within detents 118, 117 securely couple the sampler 32 tooptics housing 30 in accurate alignment and with the sampler 32 movablewith the optics housing 30. As the optics housing 30 moves relative toshell 28 and collar 26, the sizing of slots 58, 61 and 68 avoidinterference with movement of the sampler 32.

Upon initial placement of the apparatus against a patient's skin 200(FIG. 28), the ring 66 first contacts a patient's skin 200 with theneedle 10 being recessed behind the ring 66. Upon urging of theapparatus 20 against the skin 200, the ring 66 moves relative to theneedle 10 against the bias of the first spring 84. Upon achieving suchrelative movement, the needle 10 then penetrates the skin 200 with thesecond pressure surface 106 of the piston 104 engaging the skin and withboth springs 84, 86 resisting further penetration until both springs areengaged. Second spring 86 ensures a constant force acts on piston 106.

FIGS. 28-30 show a sequence of operation of the present apparatus. Asshown in FIG. 28, during the rest state, the needle 10 is recessedbehind the first pressure ring 66 to prevent damage to the needle 10 andinadvertent skin penetration. Upon initial urging of the pressure ring66 against the skin (FIG. 29), the pressure ring 66 depresses the skin200 and makes the skin taut in the area defined by the ring 66. Further,this urging of the pressure ring creates a pressurized area in the zoneof the skin layer 200 directly beneath the ring 66. This is desirablesince interstitial fluid beneath the skin 200 is believed to exist at anegative pressure. Creating a pressurized zone beneath the ring 66 isbelieved to assist in rapid collection of interstitial fluid within theneedle 10. During this initial pressurization of the skin 200, the ring66 moves relative to piston 104 until the needle 10 penetrates the skin200 and the end 106 of the piston 104 abuts the skin 200 (FIG. 30).Further depression (which can occur against soft skin but which mightnot occur against more rigid skin) is shown in FIG. 31 where the pistonend surface 106 protrudes slightly beyond the ring 66 to furtherincrease the pressure acting in the collection zone of the skin 200 andwith full penetration of the needle 10.

It has been found that this sequence of action significantly increasesthe rate at which interstitial fluid is collected through the needle 10and deposited on the membrane 12 within the sampler 32.

After full penetration of the needle 10, internal circuitry may then beactuated to operate the light source 92. Absorption of the testing lightthrough the collected sample provides an indication of the amount of theconstituent contained on the sample.

In a preferred embodiment, springs 84, 86 are preloaded. Namely, in therest position of FIGS. 1 and 28, first spring 84 exerts an urging forceon shell 28 of about three pounds and with a spring constant of aboutfour pounds per inch. Spring 86 is pre-loaded to about one pound and hasa spring constant of about two pounds per inch. To accommodate thepre-loading of springs 84, 86, optics housing 30 is provided with aretaining ring 202 (shown only in FIGS. 1 and 2) in slot 73. Thepre-loading of spring 84 insures a minimum skin pressure by ring 66before penetration of the skin 200 by needle 10.

As shown best in FIGS. 1, 2 and 18, membrane 12 is provided with aU-shaped boundary 300. Boundary 300 is formed by ultrasonically orpressure treating membrane 12 to create a material density in boundary300 which is greater than a material density of the remainder of themembrane 12. Therefore, boundary 300 provides an increased resistance toliquid flow compared to the remainder of the absorbent membrane 12. Theend 11 of needle 10 is positioned to deposit interstitial fluid onto theinterior of the U-shaped boundary 300. The increased density of theboundary 300 permits the fluid to flow within the interior of theboundary 300 but restricts fluid flow beyond the boundary 300. Thetarget location (“T”) of light through membrane 12 during testing ispositioned within the boundary 300. Boundary 300 thus insures that asufficient volume of collected fluid is in residence at the targetlocation T during testing.

It will be appreciated that through use of the present invention therate at which interstitial fluid is collected through the needle 10 isgreatly enhanced over that shown in the aforementioned InternationalPublication No. WO95/10223. Further, the sampling apparatus is containedwithin a low-cost sampler 32 which can be readily disposed after eachuse. The mating geometry of the sampler 32 with the internal geometry ofthe apparatus 20 ensures that the sampler 32 is placed within theapparatus 20 in a predetermined alignment with the sampling location inthe light path between the source 90 and the detector 92. The samplingapparatus also ensures a proper positive locking position which may bereleased easily by an operator and the entire operation of insertion ofthe sampler within the apparatus and removal of the sampler forsubsequent disposal is easily accomplished for a patient.

Having disclosed the present invention and a preferred embodiment, itwill be appreciated that modifications and equivalents of the disclosedconcepts may readily occur to one skilled in the art. It is intendedthat such modifications and equivalents shall be included within thescope of the claims which are appended hereto.

1. A sampler for collecting interstitial fluid from a skin layer, saidsampler comprising: a sampling needle having an axis and a distal end; afirst pressure surface at least partially surrounding said needle inspaced relation thereto; said needle and said first pressure surfacemovable relative to one another along a path of travel generallyparallel to said axis with said needle and said first pressure surfacehaving an extended position and a retracted position; said extendedposition characterized by said distal end of said needle extendingbeyond said first pressure surface; said retracted positioncharacterized by said distal end of said needle recessed behind saidfirst pressure surface; first biasing means for biasing said needle andsaid first pressure surface to said retracted position.
 2. A sampleraccording to claim 1 further comprising a second pressure surface atleast partially surrounding said needle and movable therewith, saidsecond pressure surface axially spaced from said distal end of saidneedle by a distance approximating a desired penetration of said needleinto said skin layer.
 3. A sampler according to claim 2 comprisingsecond biasing means for urging said needle and said second pressuresurface in a direction outwardly of said first pressure surface.
 4. Asampler according to claim 2 wherein said second pressure surface andsaid first pressure surface define a substantially continuous surfacewhen said second pressure surface and said first pressure surface are ingenerally planar alignment.
 5. A sampler according to claim 1 whereinsaid first biasing means is selected for said first pressure surface tobe urged against said skin layer with a force sufficient to define apressurized zone of interstitial fluid opposing said needle prior topenetration of said needle into said skin layer.
 6. A sampler accordingto claim 2 wherein said second pressure surface is concave.
 7. A sampleraccording to claim 1 wherein said first pressure surface is a distal endof a ring surrounding said needle in spaced relation thereto.
 8. Asampler according to claim 7 further comprising a piston surroundingsaid needle and movable therewith, said piston axially spaced from saiddistal end of said needle by a distance approximating a desiredpenetration of said needle into said skin layer.
 9. A sampler accordingto claim 8 wherein said piston and said ring are in close slidingtolerance.
 10. A sampler according to claim 9 comprising second biasingmeans for urging said needle and said piston in a direction outwardly ofsaid ring.